The goal of this project is to understand the biochemical basis of antigen-specific T cell activation and the role played by immune response genes in the regulation of this event. During the past year we have used a monoclonal antibody against the T cell antigen-specific receptor on an MHC-restricted T cell hybridoma to isolate and characterize the receptor. The molecule is a glycoprotein composed of two different polypeptide chains, each of approximately 40,000-44,000 daltons in molecular weight, that are linked together by disulfide bonds. Both chains have a core size of about 33,000 daltons after removal of sugars with endoglycosidases and appear to contain intrachain disulfide bonds. The chains differ in their isoelectric points and thus can be separated on the basis of charge. One chain was found to exist in two different molecular weight forms apparently due to differences in the level of glycosylation. In a separate set of experiments we undertook a comparison of two different mechanisms of Ir gene control, thymic selection and antigen-presentation, to determine which was dominant in the regulation of the pigeon cytochrome c T cell proliferative response of [B10.A(4R)xB10.PL]F1 mice. Using radiation-induced bone marrow chimeras it was possible to dissect out these two effects and show that the quantitative decrease in Ia molecule expression on the surface of the antigen-presenting cell was sufficient to explain the nonresponsiveness of the F1.